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Journal of Cardiology May 2024Randomized controlled trials (RCTs) have demonstrated the efficacy and safety of P2Y12 inhibitor monotherapy following short-term dual antiplatelet therapy (DAPT) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Randomized controlled trials (RCTs) have demonstrated the efficacy and safety of P2Y12 inhibitor monotherapy following short-term dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). However, no studies have compared P2Y12 inhibitor and aspirin monotherapy following short-term DAPT. We aimed to compare available strategies for DAPT duration and post-DAPT antiplatelet monotherapy following PCI.
METHODS
Seven DAPT strategies [ticagrelor or clopidogrel following 1-month DAPT, ticagrelor following 3-month DAPT, aspirin following 3-6 months of DAPT (reference strategy), aspirin or P2Y12 inhibitor following 6-18-months of DAPT, and DAPT for ≥18 months] were compared using a network meta-analysis. The primary efficacy outcome was defined as a composite of all-cause death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding.
RESULTS
Our analysis identified 25 eligible RCTs, including 89,371 patients who underwent PCI. Overall, none of the strategies negatively affected the primary efficacy outcomes. For primary bleeding outcomes, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes (HR 0.73; 95 % CI 0.57-0.95). Clopidogrel following 1-month DAPT was also associated with a reduced risk of primary bleeding outcomes (HR 0.54; 95 % CI 0.34-0.85), however, the strategy was associated with an increased risk of myocardial infarction or stent thrombosis. Similar trends were observed among patients with acute coronary syndrome and high bleeding risk.
CONCLUSIONS
Compared with aspirin monotherapy following short-term DAPT, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes without increasing any ischemic outcomes.
Topics: Humans; Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Myocardial Infarction; Network Meta-Analysis; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome
PubMed: 37562542
DOI: 10.1016/j.jjcc.2023.08.001 -
Expert Review of Cardiovascular Therapy Oct 2018Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed.
METHODS
Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: 'fractional flow reserve' AND 'nitroprusside'. Data were summarized using weighted mean differences for paired data.
RESULTS
Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) -0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02-0.30, P < 0.0001).
CONCLUSIONS
NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.
Topics: Adenosine; Coronary Stenosis; Fractional Flow Reserve, Myocardial; Humans; Nitroprusside; Vasodilator Agents
PubMed: 30122073
DOI: 10.1080/14779072.2018.1513789 -
Psychoneuroendocrinology Jan 2015It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes, measures of oxidative DNA and lipid damage respectively, are among the most reliable oxidative stress markers, but studies on their association with depression show conflicting results. This meta-analysis quantifies the association between depression and these markers and explores factors that may explain inconsistencies in the results.
METHODS
A systematic literature search was conducted in PubMed, EMBASE and PsycINFO. Studies assessing the association of 8-OHdG or F2-isoprostanes with elevated depressive symptoms, major depressive disorder (MDD) or bipolar disorder (BD) were pooled in two random-effect models.
RESULTS
The pooled effect size (Hedges' g) for the association of depression with oxidative stress was 0.31 (p=0.01, I(2)=75%) for 8-OHdG (10 studies, 1308 subjects) and 0.48 (p=0.001, I(2)=73%) for F2-isoprostanes (8 studies, 2471 subjects), indicating that both markers are increased in depression. There was no indication of publication bias for either marker. The F2-isoprostane results did not differ by type of depression, biological specimen, laboratory method or quality, however subgroup analyses in the 8-OHdG studies showed significantly stronger associations in plasma/serum vs. urine samples (p<0.01), in measurements performed with immuno-assay vs. chromatography-mass spectrometry (p<0.01) and weaker associations in high quality studies vs. low (p=0.02).
CONCLUSION
This meta-analysis finds that oxidative stress, as measured by 8-OHdG and F2-isoprostanes, is increased in depression. Larger-scale studies are needed to extend the evidence on oxidative stress in depression, and examine the potential impact of treatment.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Bipolar Disorder; Deoxyguanosine; Depression; Depressive Disorder, Major; F2-Isoprostanes; Humans; Oxidative Stress
PubMed: 25462890
DOI: 10.1016/j.psyneuen.2014.09.025 -
Progress in Neuro-psychopharmacology &... Jun 2024This systematic review and meta-analysis aimed to assess the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) in treating depression. We conducted a... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to assess the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) in treating depression. We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and ClinialTrials.gov from inception to July 3, 2023, identifying randomized controlled trials comparing SAMe with placebo or antidepressants (ADs). We synthesized data on reduced depressive symptoms (efficacy) and overall dropout rates (acceptability) using a random-effects model for pairwise frequentist meta-analysis. Our analysis included 23 trials (N = 2183) classified into three categories: 11 trials comparing SAMe and placebo, 5 trials comparing SAMe plus ADs and placebo plus ADs, and 7 trials comparing SAMe and ADs. Differences between experimental and control interventions in reducing depressive symptoms were observed: i) SAMe demonstrated significantly superior efficacy compared to placebo (SMD = -0.58, 95% CI = -0.93 to -0.23, I = 68%); ii) in conjunction with ADs, SAMe did not show a significant difference from placebo (SMD = -0.22, 95%CI = -0.63 to 0.19, I = 76%); and iii) SAMe did not exhibit a significant difference from ADs alone (SMD = 0.06, 95%CI = -0.06 to 0.18, I = 49%). No significant differences in dropout rates were observed across the three comparison categories. Moderate-certainty evidence suggests that SAMe monotherapy may offer a moderate therapeutic benefit in alleviating depressive symptoms. Considering its favorable acceptability profile, SAMe monotherapy should be considered as a treatment option for patients with depression. However, uncertainties regarding its efficacy as an adjunct to AD and its comparative efficacy with ADs remain unresolved.
Topics: Humans; S-Adenosylmethionine; Antidepressive Agents
PubMed: 38423354
DOI: 10.1016/j.pnpbp.2024.110985 -
Journal of Women's Health (2002) May 2017Oxidative stress may play an important role in both initiation and progression of breast cancer. We conducted the first systematic epidemiologic review to summarize the... (Review)
Review
BACKGROUND
Oxidative stress may play an important role in both initiation and progression of breast cancer. We conducted the first systematic epidemiologic review to summarize the published literature on oxidative stress biomarkers and breast cancer.
MATERIALS AND METHODS
We implemented systematic search strategies to identify published studies of oxidative stress biomarkers and (1) risk of developing breast cancer and (2) breast cancer prognosis using the PRISMA statement guidelines.
RESULTS
We identified eleven case-control studies of oxidative stress biomarkers and breast cancer. Biomarkers utilized varied and menopausal status was a key modifying factor. Across three nested case-control studies with biomarkers measured before diagnosis, one reported increased risk of postmenopausal breast cancer in association with 8-oxodG (DNA damage biomarker), while two (one of F-isoprostanes and one of fluorescent oxidation products) reported inverse associations for premenopausal breast cancer only. We identified eight prognostic studies. Two reported associations for lipid peroxidation and breast cancer prognosis; results for other studies were null.
CONCLUSIONS
DNA damage may increase risk of breast cancer among postmenopausal women, while lipid peroxidation may be inversely associated with premenopausal breast cancer. Lipid peroxidation may be associated with survival after breast cancer diagnosis; however, results require evaluation in large, prospective cohort studies.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers, Tumor; Breast Neoplasms; Deoxyguanosine; Female; Humans; Middle Aged; Oxidative Stress; Prognosis; Risk Factors; Survival Analysis
PubMed: 28151039
DOI: 10.1089/jwh.2016.5973 -
The Cochrane Database of Systematic... Jan 2009Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal... (Review)
Review
BACKGROUND
Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management.
OBJECTIVES
To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM).
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.
MAIN RESULTS
One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia.
AUTHORS' CONCLUSIONS
Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This review demonstrated that there is currently no evidence to suggest that alkylating agents are effective in treating Waldenstrom's macroglobulinaemia.
Topics: Alkylating Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Prednisone; Randomized Controlled Trials as Topic; Vidarabine; Waldenstrom Macroglobulinemia
PubMed: 19160296
DOI: 10.1002/14651858.CD006719.pub3 -
Drug Safety Nov 2022Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is...
INTRODUCTION
Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is scarce.
OBJECTIVE
We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatric population.
METHODS
We included original articles conducted in a paediatric population (< 18 years) in which a therapeutic intervention was described to manage APAP or idiosyncratic DILI. Findings were summarized based on age groups (preterm newborn neonates, term and post-term neonates, infants, children and adolescents).
RESULTS
Overall, 25 publications (fifteen case reports, six case series and four retrospective cohort studies) were included, including a total of 140 paediatric DILI cases, from preterm newborn neonates to adolescents. N-acetylcysteine was used to treat 19 APAP cases. N-acetylcysteine (n = 14), ursodeoxycholic acid (n = 3), corticosteroids (n = 31), carnitine (n = 16) and the combination of glycyrrhizin, reduced glutathione, polyene phosphatidylcholine and S-adenosylmethionine (n = 31) were the therapeutic options for treating idiosyncratic DILI. The molecular adsorbent recirculating system was used in the management of either APAP (n = 4) or idiosyncratic DILI (n = 2), while 20 paediatric ALF cases received continuous renal replacement therapy.
CONCLUSIONS
This systematic review identified DILI in the paediatric population who have received specific treatment. These interventions appear to be mainly extrapolated from low-quality evidence from the adult population. Thus, there is a need for high-quality studies to test the efficacy of known and novel therapies to treat DILI specifically addressed to the paediatric population. PROSPERO registration number CRD42021214702.
Topics: Acetaminophen; Acetylcysteine; Adolescent; Adrenal Cortex Hormones; Adult; Carnitine; Chemical and Drug Induced Liver Injury; Child; Drug-Related Side Effects and Adverse Reactions; Glutathione; Glycyrrhizic Acid; Humans; Infant, Newborn; Liver; Liver Failure, Acute; Retrospective Studies; S-Adenosylmethionine; Ursodeoxycholic Acid
PubMed: 36006605
DOI: 10.1007/s40264-022-01224-w -
World Journal of Gastroenterology Apr 2018To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations. (Meta-Analysis)
Meta-Analysis Review
AIM
To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.
METHODS
A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31, 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1).
RESULTS
All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.
CONCLUSION
Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.
Topics: Adenosine; Allopurinol; Disaccharides; Electrolytes; Glucose; Glutamates; Glutathione; Graft Survival; Histidine; Humans; Insulin; Liver Transplantation; Mannitol; Odds Ratio; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Primary Graft Dysfunction; Procaine; Raffinose; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome
PubMed: 29713134
DOI: 10.3748/wjg.v24.i16.1812 -
The Cochrane Database of Systematic... Jul 2006Recent trials suggest improved response rates for purine antagonists compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent trials suggest improved response rates for purine antagonists compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a survival advantage.
OBJECTIVES
To determine if there is any advantage of purine antagonists compared to alkylating agents (alone or in combination) in the treatment of patients with previously untreated B-CLL.
SEARCH STRATEGY
Medical databases (Cochrane Library, MEDLINE, EMBASE), conference proceedings and internet-based trial registers were searched electronically and/or by hand (1990-2003). All references were checked for further trial information. We also contacted experts in the field and pharmaceutical companies.
SELECTION CRITERIA
Randomised controlled trials comparing purine antagonists as single agents with alkylator-based regimens in patients with previously untreated B-CLL were included. We included full-text and abstract publications as well as unpublished data.
DATA COLLECTION AND ANALYSIS
Data extraction and quality assessment were done in duplicate by two independent reviewers. Missing data were obtained from original authors. Endpoints included overall survival, overall response rate, rate of complete remissions, progression-free survival, treatment-related morbidity and mortality.
MAIN RESULTS
Five trials with 1838 randomised patients were included. There is some evidence for improved overall survival after treatment with purine antagonists compared to alkylators, but statistical significance was not reached (HR 0.89 [95% CI 0.78-1.01], 4 trials, n=1638). However, the relative risk for achieving an overall response (RR 1.22 [95% CI 1.13-1.31], 5 trials, n=1751) and complete remission (RR 1.94 [95% CI 1.65-2.28], 5 trials, n=1751) was significantly higher, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61-0.82], 4 trials, n=1638). Incidence of grade III/IV infections was significantly higher in patients receiving treatment with purine antagonists (RR 1.83 [95% 1.30-2.58], 4 trials, n=1620). There was no significant difference concerning the relative risk for grade III/IV neutropenia (RR 1.14 [95% CI 0.98-1.34], 4 trials, n=1620) and therapy-related mortality (RR 0.94 [95% CI 0.45-1.95]). Overall incidence of hemolytic anemia was low, but significantly increased in the purine antagonist group (RR 3.36 [95% CI 1.27-8.91], 3 trials, n=1258).
AUTHORS' CONCLUSIONS
Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent purine antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and hemolytic anemia.
Topics: Antineoplastic Agents; Chlorambucil; Cladribine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Pentostatin; Randomized Controlled Trials as Topic; Vidarabine
PubMed: 16856041
DOI: 10.1002/14651858.CD004270.pub2 -
The Cochrane Database of Systematic... Apr 2006Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione, the main cellular antioxidant. Randomised clinical trials have addressed the question whether SAMe may benefit patients with alcoholic liver diseases.
OBJECTIVES
To evaluate the beneficial and harmful effects of SAMe for patients with alcoholic liver diseases.
SEARCH STRATEGY
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (1980 to May 2005), and Science Citation Index Expanded (searched May 2005).
SELECTION CRITERIA
We included randomised clinical trials studying patients with alcoholic liver diseases. Interventions encompassed per oral or parenteral administration of SAMe at any dose versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
We performed all analyses according to the intention-to-treat method using RevMan Analyses provided by the Cochrane Collaboration. We evaluated the methodological quality of the randomised clinical trials by quality components.
MAIN RESULTS
We identified nine randomised clinical trials including a heterogeneous sample of 434 patients with alcoholic liver diseases. The methodological quality regarding randomisation was generally low, but 8 out of 9 trials were placebo controlled. Only one trial including 123 patients with alcoholic cirrhosis used adequate methodology and reported clearly on all-cause mortality and liver transplantation. We found no significant effects of SAMe on all-cause mortality (relative risks (RR) 0.62, 95% confidence interval (CI) 0.30 to 1.26), liver-related mortality (RR 0.68, 95% CI 0.31 to 1.48), all-cause mortality or liver transplantation (RR 0.55; 95% CI 0.27 to 1.09), or complications (RR 1.35, 95% CI 0.84 to 2.16), but the analysis is based mostly on one trial only. SAMe was not significantly associated with non-serious adverse events (RR 4.92; 95% CI 0.59 to 40.89) and no serious adverse events were reported.
AUTHORS' CONCLUSIONS
We could not find evidence supporting or refuting the use of SAMe for patients with alcoholic liver diseases. We need more long-term, high-quality randomised trials on SAMe for these patients before SAMe may be recommended for clinical practice.
Topics: Humans; Liver Diseases, Alcoholic; Randomized Controlled Trials as Topic; S-Adenosylmethionine
PubMed: 16625556
DOI: 10.1002/14651858.CD002235.pub2